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A Study of ONCOS-102 in Combination With Other Novel Immune-therapies in Advanced Treatment-resistant Melanoma Patients

Primary Purpose

Melanoma

Status

Withdrawn

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

ONCOS-102

Balstilimab

About this trial

This is an interventional treatment trial for Melanoma focused on measuring ONCOS-102, balstilimab, checkpoint inhibitor, oncolytic virus, PD-1, PD-L1, refractory, metastatic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Be willing and able to provide written informed consent for the study.
Be ≥ 18 years of age on the day of signing the informed consent form (ICF).
Eastern Co-operative Oncology Group (ECOG) performance status 0 or 1.
Histologically confirmed diagnosis of metastatic or unresectable malignant melanoma at screening with measurable disease (by RECIST v1.1) that is accessible for IT injection into cutaneous or subcutaneous lesions.
Resistant to PD-(L)1 blockade (primary or secondary resistance in the advanced setting or relapse after adjuvant therapy) either as monotherapy or in combination with other therapies, as defined by the following criteria:
- Received at least 1 prior anti-PD-[L]1 immunotherapy regimen for a minimum of 6 weeks.
- Prior progression must be either on treatment with anti-PD-(L)1 or ≤ 12 weeks from last dose in metastatic setting or relapse ≤ 24 weeks from completion of therapy in adjuvant setting.
- Has demonstrated disease progression (PD) after anti-PD-(L)1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment (i.e., a confirmatory scan no less than 4 weeks from the date of the first documented PD), in the absence of clear clinical progression.
Has recovered from all adverse events (AEs) due to previous therapies to ≤ Grade 1 or baseline. Patients with ≤ Grade 2 endocrinopathies stable on mediation, stable neuropathy, and alopecia are eligible.

Exclusion Criteria:

Uveal or mucosal melanoma.
Any history of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 3 immune-mediated toxicity (excluding endocrinopathies and non-necrotising/bullous rash) from prior checkpoint inhibition.
• If prior severe toxicity occurred during combination treatment with anti-PD-(L)1 + anti-cytotoxic lymphocyte associated antigen 4 (CTLA-4) but subsequent treatment with anti-PD-(L)1 as monotherapy was tolerated, the patient may be eligible for inclusion after discussion with the medical monitor.
Has known (current or previously treated) central nervous system metastases and/or carcinomatous meningitis.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

ONCOS-102

ONCOS-102 and balstilimab

Arm Description

ONCOS-102 will be administered by intratumoral (IT) injection at 1.0×10^12 VP/dose with the potential to de-escalate dosing to 3.0×10^11 VP/dose.

ONCOS-102 will be administered by IT injection at 3.0×10^11 VP/dose with planned dose escalation to 1.0×10^12 VP/dose. Balsitilmab will be administered at a fixed dose of 300 mg by intravenous (IV) injection.

Outcomes

Primary Outcome Measures

Incidence of treatment-emergent adverse events [safety and tolerability] of ONCOS-102 monotherapy and ONCOS-102 plus balstilimab.

To determine the incidence of treatment emergent adverse events including treatment emergent serious adverse events assessed by CTCAE v5.0, treatment interruptions and discontinuations.

To evaluate the objective response rate (ORR) in individual cohorts using RECIST v1.1

The proportion of patients achieving confirmed complete (CR) or partial response (PR) per RECIST v1.1 criteria

Secondary Outcome Measures

To evaluate the duration of response (DoR) in individual cohorts

Time from observed objective response to first occurrence of disease progression or death based on Investigator assessment according to RECIST v1.1

To evaluate progression-free survival (PFS) in the individual cohorts using the Kaplan-Meier method

Time from treatment initiation to first occurrence of disease progression or death based on Investigator assessment according to RECIST v1.1

To evaluate overall survival (OS) in individual cohorts using the Kaplan-Meier method

Time from treatment initiation to death that occurred up to 24 months after the last patient recruited per cohort

To evaluate PFS rate estimates at 3, 6 and 12 months in individual cohorts

Proportion of patients with a partial or complete response to treatment observed at Month 3 (Month 6 and Month 12) based on RECIST v1.1

To evaluate systemic exposure of ONCOS-102

Concentration of virus particles in blood and non-compartmental PK parameters as data allow.

To estimate baseline presence and incidence of ONCOS-102 anti-drug antibodies (ADA) and neutralising antibodies (NAb) during study

ADA (screening, confirmatory results: positive or negative; titres), NAb (titres)

Full Information

NCT ID

NCT05561491

First Posted

September 27, 2022

Last Updated

June 20, 2023

Sponsor

Targovax Oy

Collaborators

Agenus Inc.

1. Study Identification

Unique Protocol Identification Number

NCT05561491

Brief Title

A Study of ONCOS-102 in Combination With Other Novel Immune-therapies in Advanced Treatment-resistant Melanoma Patients

Official Title

An Open-Label, Two-Part, Dose-Exploration and Multiple Expansion, Phase 2 Study of ONCOS-102 in Combination With Novel Immune-Targeted Anti-Cancer Agents in Patients With Unresectable or Metastatic Cutaneous Melanoma Resistant to Anti-PD-(L)1 Treatment

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Withdrawn

Why Stopped

Strategic reasons

Study Start Date

January 2024 (Anticipated)

Primary Completion Date

June 2027 (Anticipated)

Study Completion Date

June 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Targovax Oy

Collaborators

Agenus Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

A Phase 2 study investigating the efficacy and safety of ONCOS-102 alone or in combination with balstilimab (a programmed death receptor-1 [PD-1] inhibitor).

Detailed Description

This study will test ONCOS-102 in combination with novel immune-targeted anti-cancer agents in patients with unresectable or metastatic cutaneous melanoma resistant to anti-PD (L)1 treatment. The purpose of this study is to further evaluate safety and tolerability, as well as anti-tumour activity of ONCOS-102 (both as monotherapy and in combination with anti-PD-1 balstilimab) in the target population. Following a safety run-in period, up to approximately 63 participants with cutaneous melanoma who previously progressed on anti-PD-1/L1-based therapy will be allocated 1:1 to receive either ONCOS-102 alone or ONCOS-102 plus balstilimab. Part 1 - Dose Exploration Run-in: Part 1 of the study will evaluate and further optimise the dose of ONCOS-102; a recommended phase 2 dose (RP2D) for ONCOS-102 will be identified. Part 2 - Multiple Expansion: In the expansion phase, ONCOS-102 alone or in combination with balstilimab will be further evaluated in Cohorts 1 and 2 using the RP2D identified in Part 1. The study is structured to allow for additional combination cohorts to be added to the study following a protocol amendment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Melanoma

Keywords

ONCOS-102, balstilimab, checkpoint inhibitor, oncolytic virus, PD-1, PD-L1, refractory, metastatic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

2 part dose escalation and multiple expansion phase 2 trial.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ONCOS-102

Arm Type

Experimental

Arm Description

ONCOS-102 will be administered by intratumoral (IT) injection at 1.0×10^12 VP/dose with the potential to de-escalate dosing to 3.0×10^11 VP/dose.

Arm Title

ONCOS-102 and balstilimab

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

ONCOS-102

Intervention Description

Oncolytic virus

Intervention Type

Biological

Intervention Name(s)

Balstilimab

Intervention Description

Anti PD-1

Primary Outcome Measure Information:

Title

Incidence of treatment-emergent adverse events [safety and tolerability] of ONCOS-102 monotherapy and ONCOS-102 plus balstilimab.

Description

To determine the incidence of treatment emergent adverse events including treatment emergent serious adverse events assessed by CTCAE v5.0, treatment interruptions and discontinuations.

Time Frame

90 days after last treatment

Title

To evaluate the objective response rate (ORR) in individual cohorts using RECIST v1.1

Description

The proportion of patients achieving confirmed complete (CR) or partial response (PR) per RECIST v1.1 criteria

Time Frame

Up to 27 months after the last patient first dose

Secondary Outcome Measure Information:

Title

To evaluate the duration of response (DoR) in individual cohorts

Description

Time from observed objective response to first occurrence of disease progression or death based on Investigator assessment according to RECIST v1.1

Time Frame

Up to 27 months after the last patient first dose

Title

To evaluate progression-free survival (PFS) in the individual cohorts using the Kaplan-Meier method

Description

Time from treatment initiation to first occurrence of disease progression or death based on Investigator assessment according to RECIST v1.1

Time Frame

Up to 27 months after last patient recruited per cohort

Title

To evaluate overall survival (OS) in individual cohorts using the Kaplan-Meier method

Description

Time from treatment initiation to death that occurred up to 24 months after the last patient recruited per cohort

Time Frame

Up to 27 months after last patient recruited per cohort

Title

To evaluate PFS rate estimates at 3, 6 and 12 months in individual cohorts

Description

Proportion of patients with a partial or complete response to treatment observed at Month 3 (Month 6 and Month 12) based on RECIST v1.1

Time Frame

3, 6 and 12 months after last patient recruited per cohort

Title

To evaluate systemic exposure of ONCOS-102

Description

Concentration of virus particles in blood and non-compartmental PK parameters as data allow.

Time Frame

Up to 24 months after last patient in the PK sampling group

Title

To estimate baseline presence and incidence of ONCOS-102 anti-drug antibodies (ADA) and neutralising antibodies (NAb) during study

Description

ADA (screening, confirmatory results: positive or negative; titres), NAb (titres)

Time Frame

Up to 24 months after last patient in the pharmacokinetic sampling group

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Be willing and able to provide written informed consent for the study. Be ≥ 18 years of age on the day of signing the informed consent form (ICF). Eastern Co-operative Oncology Group (ECOG) performance status 0 or 1. Histologically confirmed diagnosis of metastatic or unresectable malignant melanoma at screening with measurable disease (by RECIST v1.1) that is accessible for IT injection into cutaneous or subcutaneous lesions. Resistant to PD-(L)1 blockade (primary or secondary resistance in the advanced setting or relapse after adjuvant therapy) either as monotherapy or in combination with other therapies, as defined by the following criteria: Received at least 1 prior anti-PD-[L]1 immunotherapy regimen for a minimum of 6 weeks. Prior progression must be either on treatment with anti-PD-(L)1 or ≤ 12 weeks from last dose in metastatic setting or relapse ≤ 24 weeks from completion of therapy in adjuvant setting. Has demonstrated disease progression (PD) after anti-PD-(L)1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment (i.e., a confirmatory scan no less than 4 weeks from the date of the first documented PD), in the absence of clear clinical progression. Has recovered from all adverse events (AEs) due to previous therapies to ≤ Grade 1 or baseline. Patients with ≤ Grade 2 endocrinopathies stable on mediation, stable neuropathy, and alopecia are eligible. Exclusion Criteria: Uveal or mucosal melanoma. Any history of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 3 immune-mediated toxicity (excluding endocrinopathies and non-necrotising/bullous rash) from prior checkpoint inhibition. • If prior severe toxicity occurred during combination treatment with anti-PD-(L)1 + anti-cytotoxic lymphocyte associated antigen 4 (CTLA-4) but subsequent treatment with anti-PD-(L)1 as monotherapy was tolerated, the patient may be eligible for inclusion after discussion with the medical monitor. Has known (current or previously treated) central nervous system metastases and/or carcinomatous meningitis.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Douglas B Johnson, MD, MSCI

Organizational Affiliation

Vanderbilt Institute for Infection, Immunology and Inflammation

Official's Role

Principal Investigator

12. IPD Sharing Statement

Learn more about this trial

A Study of ONCOS-102 in Combination With Other Novel Immune-therapies in Advanced Treatment-resistant Melanoma Patients

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